From the Guidelines
The first-line treatment for Chronic Myeloid Leukemia (CML) should be a tyrosine kinase inhibitor (TKI), with generic imatinib being the cost-effective initial treatment in chronic phase (CP) patients, as recommended by the European LeukemiaNet 2020 guidelines. The therapeutic landscape of CML has changed significantly over the past few years, with most patients now having a normal life expectancy 1. The primary goal of treatment is to achieve a stable deep molecular response (DMR) and discontinuing medication for treatment-free remission (TFR). Key considerations in treating CML include:
- Assessing patient risk status at diagnosis using the new EUTOS long-term survival (ELTS)-score 1
- Monitoring response through quantitative polymerase chain reaction whenever possible 1
- Considering various contraindications and side-effects of all TKIs 1
- Changing treatment when intolerance cannot be ameliorated or when molecular milestones are not reached, such as greater than 10% BCR-ABL1 at 3 months indicating treatment failure 1 Other treatment options, such as allogeneic transplantation, may be considered for advanced phase CML or patients who fail multiple TKI therapies 1. It is essential to withhold TKI treatment during pregnancy and consider treatment discontinuation in patients with durable DMR to achieve TFR 1.
From the Research
Definition and Incidence of CML
- Chronic Myeloid Leukemia (CML) is a myeloproliferative neoplasm with an incidence of 1-2 cases per 100,000 adults 2, 3.
- It accounts for approximately 15% of newly diagnosed cases of leukemia in adults 2, 3.
- CML has an annual incidence of 2 cases per 100,000 people, with approximately 150,000 people in the US and 5 million worldwide having CML 4.
Characteristics of CML
- CML is characterized by a balanced genetic translocation, t(9;22) (q34;q11.2), involving a fusion of the Abelson gene (ABL1) from chromosome 9q34 with the breakpoint cluster region (BCR) gene on chromosome 22q11.2 2, 3.
- This rearrangement is known as the Philadelphia chromosome, resulting in the generation of a BCR::ABL1 fusion oncogene and a BCR::ABL1 oncoprotein 2, 3.
Treatment Options for CML
- Four tyrosine kinase inhibitors (TKIs), imatinib, dasatinib, bosutinib, and nilotinib, are approved by the United States Food and Drug Administration for first-line treatment of newly diagnosed CML in chronic phase (CML-CP) 2, 3.
- Second-line options include second and third-generation TKIs, such as ponatinib, asciminib, and olverembatinib, for patients who develop resistance to first-line therapy 2, 3.
- Allogeneic stem cell transplantation remains an important therapeutic option for patients with CML-CP and failure of at least two TKIs, and for all patients in advanced-phase disease 2, 4, 3.
Treatment Outcomes and Adverse Effects
- Clinical trials with second-generation TKIs reported significantly deeper and faster responses, but had no impact on survival prolongation 2, 3.
- TKIs are associated with hematologic toxicity, such as myelosuppression, and additional agent-specific adverse effects, such as pleural effusion, arterio-occlusive events, and gastrointestinal disturbance 4, 5.
- Medication adherence is important to maintain treatment responsiveness, and TKI therapy should be selected with consideration of adverse effects 4, 5.